title: Transgenic 6F tomatoes act on the small intestine to prevent systemic inflammation and dyslipidemia caused by Western diet and intestinally derived lysophosphatidic acid.
abstract: We recently reported that levels of unsaturated lysophosphatidic acid (LPA) in the small intestine significantly correlated with the extent of aortic atherosclerosis in LDL receptor-null (LDLR⁻/⁻) mice fed a Western diet (WD). Here we demonstrate that WD increases unsaturated (but not saturated) LPA levels in the small intestine of LDLR⁻/⁻ mice and causes changes in small intestine gene expression. Confirmation of microarray analysis by quantitative RT-PCR showed that adding transgenic tomatoes expressing the apoA-I mimetic peptide 6F (Tg6F) to WD prevented many WD-mediated small intestine changes in gene expression. If instead of feeding WD, unsaturated LPA was added to chow and fed to the mice: i) levels of LPA in the small intestine were similar to those induced by feeding WD; ii) gene expression changes in the small intestine mimicked WD-mediated changes; and iii) changes in plasma serum amyloid A, total cholesterol, triglycerides, HDL-cholesterol levels, and the fast-performance liquid chromatography lipoprotein profile mimicked WD-mediated changes. Adding Tg6F (but not control tomatoes) to LPA-supplemented chow prevented the LPA-induced changes. We conclude that: i) WD-mediated systemic inflammation and dyslipidemia may be in part due to WD-induced increases in small intestine LPA levels; and ii) Tg6F reduces WD-mediated systemic inflammation and dyslipidemia by preventing WD-induced increases in LPA levels in the small intestine.
authors.affiliation: Departments of Medicine, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA 90095.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Navab
authors.forename: Greg
authors.initials: G
authors.lastname: Hough
authors.forename: Georgette M
authors.initials: GM
authors.lastname: Buga
authors.forename: Feng
authors.initials: F
authors.lastname: Su
authors.forename: Alan C
authors.initials: AC
authors.lastname: Wagner
authors.forename: David
authors.initials: D
authors.lastname: Meriwether
authors.forename: Arnab
authors.initials: A
authors.lastname: Chattopadhyay
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Victor
authors.initials: V
authors.lastname: Grijalva
authors.forename: Janet S
authors.initials: JS
authors.lastname: Danciger
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Van Lenten
authors.forename: Elin
authors.initials: E
authors.lastname: Org
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Calvin
authors.initials: C
authors.lastname: Pan
authors.forename: G M
authors.initials: GM
authors.lastname: Anantharamaiah
authors.forename: Robin
authors.initials: R
authors.lastname: Farias-Eisner
authors.forename: Susan S
authors.initials: SS
authors.lastname: Smyth
authors.forename: Srinivasa T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Alan M
authors.initials: AM
authors.lastname: Fogelman
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D004032:Diet / Q000009:adverse effects*; D050171:Dyslipidemias / Q000097:blood / Q000209:etiology* / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism*; D018551:Solanum lycopersicum / Q000235:genetics*; D008246:Lysophospholipids / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D057786:Peptidomimetics / Q000378:metabolism*; D030821:Plants, Genetically Modified; D011973:Receptors, LDL / Q000172:deficiency; D019366:Western World
chemical_list: D016632:Apolipoprotein A-I; D008246:Lysophospholipids; D057786:Peptidomimetics; D011973:Receptors, LDL; C032881:lysophosphatidic acid
keywords: 6F peptide; apolipoprotein A-I mimetic peptides; atherosclerosis; genetically engineered tomato plants; lysophosphatidic acid